Best Andrew, Dagliesh Caroline, Ehrmann Ingrid, Kheirollahi-Kouhestani Mahsa, Tyson-Capper Alison, Elliott David J
Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK.
Int J Cell Biol. 2013;2013:843781. doi: 10.1155/2013/843781. Epub 2013 Jul 8.
The splicing regulator proteins SRSF1 (also known as ASF/SF2) and SRSF3 (also known as SRP20) belong to the SR family of proteins and can be upregulated in cancer. The SRSF1 gene itself is amplified in some cancer cells, and cancer-associated changes in the expression of MYC also increase SRSF1 gene expression. Increased concentrations of SRSF1 protein promote prooncogenic splicing patterns of a number of key regulators of cell growth. Here, we review the evidence that upregulation of the SR-related Tra2 β protein might have a similar role in cancer cells. The TRA2B gene encoding Tra2 β is amplified in particular tumours including those of the lung, ovary, cervix, stomach, head, and neck. Both TRA2B RNA and Tra2 β protein levels are upregulated in breast, cervical, ovarian, and colon cancer, and Tra2 β expression is associated with cancer cell survival. The TRA2B gene is a transcriptional target of the protooncogene ETS-1 which might cause higher levels of expression in some cancer cells which express this transcription factor. Known Tra2 β splicing targets have important roles in cancer cells, where they affect metastasis, proliferation, and cell survival. Tra2 β protein is also known to interact directly with the RBMY protein which is implicated in liver cancer.
剪接调节蛋白SRSF1（也称为ASF/SF2）和SRSF3（也称为SRP20）属于SR蛋白家族，在癌症中可上调。SRSF1基因本身在一些癌细胞中扩增，MYC表达的癌症相关变化也会增加SRSF1基因的表达。SRSF1蛋白浓度的增加会促进许多细胞生长关键调节因子的促癌剪接模式。在此，我们综述了SR相关Tra2β蛋白上调可能在癌细胞中具有类似作用的证据。编码Tra2β的TRA2B基因在包括肺癌、卵巢癌、宫颈癌、胃癌、头颈癌在内的特定肿瘤中扩增。TRA2B RNA和Tra2β蛋白水平在乳腺癌、宫颈癌、卵巢癌和结肠癌中均上调，且Tra2β表达与癌细胞存活相关。TRA2B基因是原癌基因ETS-1的转录靶点，ETS-1可能导致在某些表达该转录因子的癌细胞中出现更高水平的表达。已知的Tra2β剪接靶点在癌细胞中具有重要作用，它们在其中影响转移、增殖和细胞存活。Tra2β蛋白还已知与涉及肝癌的RBMY蛋白直接相互作用。
